title: Radionuclide antibody-conjugates, a targeted therapy towards cancer.
abstract: Targeted alpha therapy (TAT) is an investigational procedure which utilises monoclonal antibodies (mAbs), peptide conjugates and/or other chemical compounds. These bio-vectors are able to transport a dose of alpha particles to destroy cancer cells. Radionuclide antibody-conjugates (RACs), labelled with beta emitters, have already been used in humans. More recently, TAT has been introduced to treat oncological diseases mainly leukaemia and lymphoma. Encouraging results have also been obtained in solid neoplasms with the administration of anti-tenascin. This chimeric antibody labelled with astatine-211 was delivered in patients with recurrent brain tumours into a surgically created cavity. Conversely, a clinical trial using a standard TAT approach to treat patients with metastatic melanoma, observed the shrinkage of the solid tumour mass. This response in melanoma may lead to an alternative mechanism for TAT, called tumour-antivascular- alpha-therapy (TAVAT), and forms the basis of a novel approach to the treatment of cancer disease states. In this paper, we will concentrate mainly on the application of TAT using antibodies. In particular, an investigation into the major general features connected with the use of alpha emitters in cancer therapy will be discussed. The prospective role of TAT with RACs will also be outlined briefly, especially focussing on the most important therapeutic strategies to date based on antibodies radiolabelled with beta emitters.
authors.affiliation: Department of Biocatalysis and Isotope Chemistry, Almac, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD, United Kingdom. sean.kitson@almacgroup.com
authors.forename: Sean L
authors.initials: SL
authors.lastname: Kitson
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuccurullo
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Moody
authors.forename: Luigi
authors.initials: L
authors.lastname: Mansi
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000532:radiotherapy / Q000556:secondary; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008545:Melanoma / Q000532:radiotherapy; D009362:Neoplasm Metastasis / Q000532:radiotherapy; D009369:Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011876:Radionuclide Generators; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000532:radiotherapy
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000922:Immunotoxins; D019275:Radiopharmaceuticals; C422802:ibritumomab tiuxetan; C119496:tositumomab I-131